Synthesis and testing of novel phenyl substituted side-chain analogues of classical cannabinoids

A series of novel phenyl substituted side-chain analogues of classical cannabinoids were synthesized and their CB I and CB2 binding affinities were evaluated relative to Delta(8)-THC and compound 2. CB1 and CB2 binding assays indicate that the dimethyl and ketone analogues (3) and (6) display selectivity for the CB2 receptor in comparison to Delta(8)-THC and compound 2. This study provides newer insights into the geometrical and functional group requirements of the ligand binding pockets of the CB1 and the CB2 receptors. (C) 2003 Elsevier Ltd. All rights reserved.